Evaluation of a Balloon Occlusion and Aspiration System for Protection from Distal Embolization During Stenting in Saphenous Vei

Eberhard Grube, MD, Jürgen Schofer, MD, John Webb, MD, Gerhard Schuler, MD, Antonio Colombo, MD, Horst Sievert, MD, Ulrich Gerckens, MD, Gregg W. Stone, MD, for the Saphenous Vein Graft Angioplasty Free of Emboli (SAFE) Trial Study Group
Eberhard Grube, MD, Jürgen Schofer, MD, John Webb, MD, Gerhard Schuler, MD, Antonio Colombo, MD, Horst Sievert, MD, Ulrich Gerckens, MD, Gregg W. Stone, MD, for the Saphenous Vein Graft Angioplasty Free of Emboli (SAFE) Trial Study Group
ABSTRACT: Distal embolization after angioplasty in degenerated saphenous vein grafts (SVGs) results in high rates of periprocedural myonecrosis and mortality. Temporary protection of the distal microcirculation with aspiration of dislodged debris may improve the safety of SVG intervention. To evaluate the feasibility, safety and efficacy of distal protection using the PercuSurge GuardWire Occlusion and Aspiration System, 103 consecutive patients undergoing planned stenting of 105 SVG lesions were prospectively enrolled in a multinational, multicenter study. Before angioplasty, protection of the distal circulation was achieved with the PercuSurge GuardWire distal balloon occlusion system, followed by stenting and debris aspiration. Quality assurance measures in the study included independent on-site data monitoring, clinical event adjudication, data analysis and use of multiple core laboratories. Mean graft age was 8.9 ± 4.0 years. The duration of distal balloon inflation was 5.4 ± 3.7 minutes; premature balloon deflation for ischemia was not required in any patient. Macroscopically visible red and/or yellow debris was extracted in 91% of patients. By core lab analysis, postprocedural Thrombolysis In Myocardial Infarction-III flow was present in 98.9% of grafts (versus 83.5% before intervention). No patient developed angiographic evidence of no reflow or distal embolization. Postprocedural creatine phosphokinase MB isozyme levels were elevated to > 3 times normal in only 5 patients (5%), and 97 patients (94%) were free of major adverse events at 30 days. We conclude that the GuardWire distal balloon occlusion and aspiration system is an effective and safe method for protecting distal microcirculation from the adverse consequences of embolization during mechanical intervention of degenerated SVGs. The PercuSurge GuardWire (PercuSurge, Inc., Sunnyvale, California) balloon occlusion system1,2 was designed to provide protection of the distal microcirculation during percutaneous intervention by temporarily occluding the distal vessel during angioplasty, thereby facilitating aspiration of dislodged atheromatous and thrombotic material before it reached the arteriolar and capillary bed. A previous single-center study in 27 patients reported favorable results with this device as an adjunct to percutaneous intervention in saphenous vein grafts (SVGs).2 Whether these results can be generalized to multiple centers and operators is unknown. We investigated the feasibility, safety and efficacy of GuardWire use during SVG intervention in a prospective, controlled, international, multicenter registry before performance of a pivotal randomized trial. Methods Consecutive eligible patients requiring stenting of 1 or 2 lesions in a single SVG were enrolled at 10 international sites in Germany, Italy and Canada. Inclusion criteria were age >18 years; evidence of symptomatic or inducible ischemia; SVG reference vessel diameter >= 3 mm and = 50% and = 20 mm of normal vessel distal to the target lesion for placement of the occlusion balloon. Patients were excluded for contraindications or allergy to heparin, aspirin, or thienopyridine agents; acute myocardial infarction (AMI) or recent AMI within 24 hours; planned multivessel or staged intervention within 30 days of the procedure; target lesion at the aorto-ostium or after the first anastomosis in a jump graft; left ventricular ejection fraction 2.5 mg/dl; comorbid conditions limiting anticipated survival to Device and procedure description. The PercuSurge GuardWire Occlusion and Aspiration System is composed of 3 principal components:1,2 the GuardWire™ Temporary Occlusion Catheter, the MicroSeal™ Adapter, and the Export™ Aspiration Catheter (PercuSurge, Inc.). The GuardWire consists of an elastomeric balloon attached distally to a 0.014-inch guidewire incorporating a central inflation lumen, with distal balloon diameters ranging from 3.0–6.0 mm (Figure 1). The low profile of the deflated balloon (0.036 inches) facilitates lesion crossing without embolization. Injection of diluted contrast through the wire results in temporary inflation of the distal occlusion balloon at low pressure, which is positioned several centimeters beyond the stenosis. Actuating the MicroSeal adapter then closes a proximal valve in the GuardWire, allowing the inflation syringe to be disconnected without balloon deflation, after which intervention is performed over the wire with any 0.014-inch compatible device. Atherosclerotic and thrombotic debris is then aspirated through the 5 Fr monorail export catheter (Figure 1), the GuardWire balloon is deflated, and flow is restored. All patients were pretreated with >= 100 mg of aspirin and >= 250 mg of ticlopidine beginning on the day of the procedure. An activated clotting time was maintained at > 300 seconds during intervention. Patients with stents received ticlopidine 250 mg twice daily for 2–4 weeks and aspirin indefinitely. Electrocardiograms were obtained before and after angioplasty. Serial creatine phosphokinase (CPK)-MB levels were measured at baseline and every 8 hours for 24 hours after the procedure. Endpoints and definitions. The prespecified primary endpoint of the study was the in-hospital rate of any major adverse cardiac event, defined as death, Q-wave or non-Q wave AMI (peak CPK-MB >= 3 times normal), emergent bypass surgery or repeat percutaneous target vessel revascularization. Major secondary endpoints included the incidence of “no-reflow” (TIMI 0–1 flow in patients with prior TIMI 2–3 flow), device success, lesion success and adverse events at 30 days. Device success was defined as successful deployment of the GuardWire, occlusion of flow, and performance of aspiration. Lesion success was defined as attainment of 8 times normal in 2 patients (2%). One in-hospital death resulted from ventricular fibrillation subsequent to a Q-wave myocardial infarction not related to the target vessel intervention. Morphometric and histologic analysis. Grossly visible red and/or yellow debris was extracted from 94 patients (91%) (Figure 2). Histologic examination revealed evidence of fibrin and necrotic core in 100% of specimens, foam cells in 80% and cholesterol clefts in 29% of specimens. Scanning electron microscopy documented particles ranging from 17–807 microns in diameter (Figure 3). DiscussionDistal embolization is a frequent complication of percutaneous intervention in degenerated SVGs, resulting in CPK-MB elevations in as many as 32% of patients.3–6 In addition to mechanical obstruction of distal flow, thromboxane-induced vasomotor changes, free radical generation, neutrophilic plugging and local myocardial edema may attend embolization and contribute to myonecrosis.7–12 Severe embolization may result in the no-reflow phenomenon, the occurrence of which is associated with a 15% rate of mortality and a 31% risk of AMI.13 Neither prolonged intracoronary infusion of urokinase, glycoprotein IIb/IIIa inhibitors, directional atherectomy or aspiration thrombectomy with the transluminal extraction catheter or the AngioJet (Possis Medical, Minneapolis, Minnesota) have conclusively been demonstrated to safely improve early and late clinical outcomes after SVG stenting, although the thrombectomy devices may improve acute results.3,14–21 As demonstrated in the present prospective multicenter study, the PercuSurge emboli containment system may be safely incorporated into the percutaneous management of SVG lesions, and facilitated successful stent implantation with periprocedural AMI and 30-day major adverse events occurring in only 4.9% and 5.8% of patients, respectively, significantly lower than anticipated from historical controls.3–6,15–21 Histologic analysis confirmed that distal balloon occlusion and aspiration is capable of extracting large amounts of thrombus or particulate debris from degenerated SVGs undergoing angioplasty. On the basis of this study, the large randomized pivotal SVG Angioplasty Free of Embolic Randomized (SAFER) trial was performed to definitively demonstrate the effectiveness of distal protection with the PercuSurge system as an adjunct to SVG intervention. The concern that the 3–6 minutes of compulsory distal occlusion may not be tolerated in some patients because of severe angina, hypotension or rhythm instability was not substantiated in this study. No patient required premature balloon deflation. However, few patients were treated with severe left ventricular dysfunction, a situation in which this duration of ischemia may not be hemodynamically tolerated, or require intra-aortic balloon support. Furthermore, although neither severe graft injury nor perforation resulted from the distal occlusion balloon in this series, close attention must be paid to ensuring the proper placement and sizing of the device, especially given the requirement for at least 20 mm of uninvolved vessel present after the lesion but before the distal anastomosis to accommodate the balloon. Compared with standard angioplasty guidewires, the GuardWire is somewhat stiffer, and transmits torque less effectively. Furthermore, the deflated balloon profile, although only 0.036 inches in diameter, may still impede crossing of a tight stenosis and theoretically contribute to distal embolization. As a result, successful deployment of the device and aspiration was achieved in only 85% of lesions. A significant learning curve is also present with this device. These factors, in addition to incomplete aspiration and improper positioning, may have contributed to the observation that myonecrosis still developed in 9% of patients. The next generation of the GuardWire, in which the profile has been reduced to 0.028 inches and the shaft re-engineered to enhance steering, will likely further increase device success and improve patient outcomes. In contrast to the PercuSurge distal balloon occlusion and aspiration system, a variety of distal filters have been developed that are currently undergoing investigation. With pore sizes ranging from 80–150 µm, filters offer the potential advantage of permitting anterograde blood flow during the procedure. Theoretical drawbacks to these devices, however, include an inherently larger crossing profile, unhindered embolization of smaller particles and vasoactive substances, overloading of the filter with embolized debris (with subsequent reduced perfusion or nonretained material), a higher profile required for device retraction, and difficulty in withdrawing all captured material without dislodgement. Comparative trials are underway to determine the relative safety and efficacy of these competing technologies. Similarly, whether distal protection is more effective than suction aspiration or rheolytic thrombectomy, or whether selected patients may synergistically benefit from thrombectomy with concurrent distal protection deserves further study. Finally, the experience described herein applies only to intervention of SVGs; further investigation is needed to evaluate the role of distal protection during angioplasty of other vascular beds (e.g., native coronary, carotid and renal arteries) and in other clinical scenarios (e.g., AMI).
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